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NP08 & NP09: Lectures 8 & 9 Nutritional Physiology: Gluconeogenesis and Pentose Phosphate Pathway (PPP) + Amino acid catabolism: N and C metabolism

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NP08 & NP09: Lectures 8 & 9 Nutritional Physiology NP08 – Gluconeogenesis and Pentose Phosphate Pathway (PPP) NP09 – Amino acid catabolism: N and C metabolism

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NP08 – Gluconeogenesis and Pentose Phosphate Pathway (PPP)
Pentose Phosphate Pathway (NADPH)
Pentose Phosphate cycle = hexose monophosphate shunt = pentose phosphate pathway (PPP)
Happening in the cytoplasm it’s a specific sidestep of the glycolysis




Specifically made to produce NADPH
We start with an intermediate of glycolysis (glucose-6-P = substrate) and we end with intermediates of
glycolysis (fructose-6-P and glyceraldehyde 3-phosphate = end products)

Nicotinamide nucleotide coenzymes: NAD and NADP
NADPH is needed for fatty acid synthesis
In NADP: OH group is phosphorylated

Steps of PPP in detail
We produce 2 NADPH
Substrate of PPP is glucose-6-phosphate à we need 3 G6P for the whole pathway

PPP uses 3 moles of glucose-6-phosphate as input: linked to the reduction of 6 moles of NADP+ to NADPH
PPP produces:
§ 2 moles of fructose-6-phosphate (intermediate of glycolysis)
§ 1 mole of glyceraldehyde-3-phosphate (intermediate of glycolysis)
§ 3 moles of carbon dioxide CO2

= The source of 50% of the NADPH needed for fatty acid synthesis (highly relevant if you start from glucose and
want to store it as TAG)
The only source of NADPH in red blood cells (it fully relies on cytoplasmic …… because RBC lack mitochondria)
The pathway for synthesis of 5-carbon sugars
3 G-6-P à 2 F-6-P + GA3P + 6 NADPH + 3 CO2 (exhaled)

Comparison between PPP and glycolysis
What is the benefit of cells to switch from glycolysis to PPP (so instead of getting ATP from glycolysis)
PPP: 3 G-6-P à 2 F-6-P + GA3P + 6 NADPH + 3 CO2
Glycolysis: 2 G-6-P à 2 F-6-P
1 G-6-P à 2 mole GA3P – 1 ATP (you invest 1 single ATP)
1 mole GA3P for complete oxidation: + 3.5 (GA3P à pyruvate) + 12.5 ATP = 16 ATP (+ 3 CO2)
è total: 3 G-6-P à 2 F-6-P + GA3P + 15 ATP (+ 3 CO2)

The cell has to decide at the level of G-6-P what is going to happen
à PPP is chosen when there is abundance of energy present = PPP for NADPH synthesis and fatty acid
synthesis
à If the cell is in need of ATP/energy: glycolysis and ATP

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